Brain imaging is used to study cerebral metabolic correlates of drug abuse. PET scans of human subjects show that euphoriants reduce global and regional cerebral metabolic rate(s) for glucose (CMRglc and rCMRglc, respectively); rCMRglc correlates with subjective effects. The extent to which temporal pole rCMRglc determines drug-induced euphoria is studied. Drug abusers differ from controls in occipital cortical rCMRglc and personality measures. AIDS patients are tested before and after peptide T therapy to obtain information about neurocognitive deficits in AIDS and peptide T as a treatment. X-ray computed tomography and magnetic resonance imaging are used to study brain structure, as related to drug abuse. Substance abusers show deficits in linear measures. Ventricle-brain ratio (VBR) correlates with age (from 3rd - 6th decades of life) in drug abusers. The intensity of cocaine's subjective effects correlates negatively with VBR. Reduced sensitivity to subjective effects of cocaine in subjects with large VBR suggests changes in brain regions that mediate these subjective effects. Studies of rCMRglc in rats are used to map responses to psychoactive drugs. d-N-Allylnormetazocine, a sigma receptor ligand produces dose-dependent responses, reflecting affinities of the drug for sigma and PCP receptors. Effects of low doses manifest coupling of sigma receptors to brain function. CI943, which lacks sigma receptor activity, but was under investigation as a potential atypical antipsychotic, produces responses similar to those of other antipsychotics, except in the extrapyramidal system, consistent with a paucity of extrapyramidal side effects of CI943. To extend work on cerebral hypermetabolism during opioid withdrawal, rCMRglc is tested in M-dependent rats. Methylnaloxonium (MN), an opioid antagonist, is injected into the locus ceruleus or central amygdala to evaluate contributions of these loci to hypermetabolism. We evaluated [125-I]l-(p-iodophenyl)-3-(l-adamantyl)guanidine (PIPAG) as a ligand for sigma receptors. PIPAG binds to sigma receptors selectively and with high affinity. PIPAG binding, assayed autoradiographically, parallels that of other sigma ligands. The use of this ligand for SPECT imaging warrants study.